Clinical trials for Molgradex

Clinical trials for Molgradex

Molgradex is an inhaled formulation of recombinant human GM-CSF that is being developed for the treatment of autoimmune pulmonary alveolar proteinosis, or PAP, a rare lung disease characterized by the build-up of lung surfactant in the alveoli, or air sacs, of the lungs.

Molgradex Phase 3 Pivotal Study (worldwide) (IMPALA)

Savara’s pivotal phase II/III clinical trial is named IMPALA

Savara is currently conducting a clinical study of Molgradex worldwide in PAP patients.

The aim of this randomized, double-blind, placebo-controlled study is to compare efficacy and safety of Molgradex with placebo. In the study, patients are randomized to receive treatment via inhalation for up to 24 weeks in one of three treatment arms: 1) Molgradex 300 µg administered once daily, 2) Molgradex 300 µg and matching placebo administered daily in 7-day intermittent cycles of each, or 3) inhaled placebo administered once daily.

The primary endpoint is the absolute change from baseline of arterial-alveolar oxygen gradient ((A-a)DO2) after 24 weeks of treatment. This endpoint is a measure of patient’s oxygenation status, and the endpoint value is expected to decrease as the physical obstacle of gas exchange is reduced by clearance of excess surfactant from the lungs. Key secondary endpoints that will be assessed to show improvement in clinical symptoms and function, including six-minute walk distance, St. George’s respiratory questionnaire, and the time to need of whole lung lavage.

Phase I trial in healthy volunteers

Savara has finalized and received data from phase I clinical trial – a randomized, double-blind, placebo-controlled, single-center, single-ascending dose (SAD) and multiple ascending-dose (MAD) study. Its objectives were to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of molgramostim when administered by inhalation to healthy adult subjects.

The trial enrolled 42 healthy adults and was conducted by Celerion in Belfast, Northern Ireland. Initial data from the trial were published October 2015.

Drug formulation was well tolerated at all dose levels; no serious or severe treatment emergent adverse events were registered.

None of the subjects developed antibodies against Molgradex.

Number of Molgradex treated subjects reporting treatment emergent adverse events was similar to that seen in placebo.

The number of related treatment emergent adverse events per subject was higher in Molgradex treated subjects (2.1 per subject in the active group >< 1.4 per subject in the placebo group).

Mild cough was the most frequently related adverse event. The number of subjects reporting any treatment emergent adverse events was similar to that seen in placebo.

The number of treatment related cough events per subject was higher in Molgradex treated subjects (1.6 per subject in the active group >< 1.25 in the placebo group).

In line with the expected efficacy of GM-CSF 28/30 subjects in the Molgradex groups reported a mild increase of white blood cell counts characterized as ‘not clinically significant’.

In two subjects the increase of white blood cell counts were reported as ’mild adverse events’.

The concentration of Molgradex measured in the blood after inhalation was 50-100 times lower than after systemic administration of GM-CSF.

The results of the phase I clinical trial were presented at ATS (American Thoracic Society) congress in May 2016. Scientific poster attached.